Metabolic transistor in bacteria
The disclosure relates to a metabolic transistor in bacteria where a competitive pathway is introduced to compete with a product pathway for available carbon so as to control the carbon flux in the bacteria.
1. A method of increasing the production of a product in a bacteria, said method comprising:
a) providing a bacteria having a product pathway producing a product, wherein a competitive pathway competes with said product pathway for available carbon, said competitive pathway requiring a cofactor that is not rate limiting;
b) introducing one or more diverting gene(s) under the control of a promoter into said bacteria to directly or indirectly divert said cofactor or an intermediate in the formation of the cofactor away from said competitive pathway;
c) allowing expression of said diverting gene(s) and reducing levels of said cofactor, and thus reducing levels of said competitive pathway;
d) thereby increasing said product pathway and said product;
wherein said cofactor and said one or more diverting genes and said products are selected from the group consisting of:
Cofactor:
Diverting gene(s) encoding:
Product:
ubiquinone
geranylgeranyl diphosphate
Fermentative products or
synthase and phytoene
lactate or acetate ethanol or
synthase and phytoene
formate, or acetate or
desaturase
succinate or 2,3 butane diol
ubiquinone
geranyl diphosphate: 4-
Fermentative products or
hydroxybenzoate
lactate or acetate ethanol or
geranyltransferase
formate, or acetate or
succinate or 2,3 butane diol
biotin
Biotin-CoA ligase or biotin
Glutamate or lysine
CoA synthetase
pantothenate
pantothenate hydrolyase
Valine
thiamine
thiamine pyridinylase or
Fermentative products or
aminopyrimidine
lactate or ethanol or formate,
aminohydrolase
or acetate or succinate or 2,3
butane diol pr
Folate or 4-
4-aminobenzoate 1-
Serine
amino-
monooxygenase or
benzoate
aminobenzoate
decarboxylase
Heme
Siroheme synthase
Fermentative products or
lactate or acetate ethanol or
formate or acetate or succinate
or 2,3 butane diol
3-Methyl-2-
2-oxoisovalerate
PHE or TYR.
oxobutanoic
dehydrogenase or 3-methyl-
acid
2-oxobutanoate
dehydrogenase
2. The method of claim 1 , wherein said promoter is a constitutive promoter.
3. The method of claim 1 , wherein said promoter is an inducible promoter.
4. The method of claim 1 , wherein said bacteria is E. coli or Corynebacterium glutamicum.
5. The method of claim 1 , wherein said cofactor is ubiquinone and said diverting gene(s) is i) crtE, crtB and crtI or ii) PGT-1.
6. The method of claim 1 , wherein said cofactor is heme and said diverting gene(s) encodes siroheme synthase.
7. The method of claim 1 , wherein said cofactor is thiamine and said diverting gene(s) encodes thiamine pyridinylase or aminopyrimidine aminohydrolase.